Hydroxy nitriles

The zwitterion (6) can react with protic solvents to produce a variety of products. Reaction with water yields a transient hydroperoxy alcohol (10) that can dehydrate to a carboxyUc acid or spHt out H2O2 to form a carbonyl compound (aldehyde or ketone, R2CO). In alcohoHc media, the product is an isolable hydroperoxy ether (11) that can be hydrolyzed or reduced (with (CH O) or (CH2)2S) to a carbonyl compound. Reductive amination of (11) over Raney nickel produces amides and amines (64). Reaction of the zwitterion with a carboxyUc acid to form a hydroperoxy ester (12) is commercially important because it can be oxidized to other acids, RCOOH and R COOH. Reaction of zwitterion with HCN produces a-hydroxy nitriles that can be hydrolyzed to a-hydroxy carboxyUc acids. Carboxylates are obtained with H2O2/OH (65). The zwitterion can be reduced during the course of the reaction by tetracyanoethylene to produce its epoxide (66). 

A cyanohydrin is an organic compound that contains both a cyanide and a hydroxy group on an aUphatic section of the molecule. Cyanohydrias are usually a-hydroxy nitriles which are the products of base-cataly2ed addition of hydrogen cyanide to the carbonyl group of aldehydes and ketones. The lUPAC name for cyanohydrias is based on the a-hydroxy nitrile name. Common names of cyanohydrias are derived from the aldehyde or ketoae from which they are formed (Table 1). 

Cyanohydrins are highly toxic by inhalation or ingestion, and moderately toxic through skin absorption (21). AH a-hydroxy nitriles are potential sources of hydrogen cyanide or cyanides and must be handled with considerable caution. Contact with the skin and inhalation should be rigorously avoided. Special protective clothing should be worn and any exposure should be avoided (18,20). The area should be adequately ventilated. Immediate medical attention is essential in case of cyanohydrin poisoning. 

Huonnations with DAST proceed with high chemoselectivity In general, under very mild reaction conditions usually required for the replacement of hydroxyl groups, other functional groups, including phenolic hydroxyl groups [112], remain intact This provides a method for selective conversion of hydroxy esters [95 97] (Table 6), hydroxy ketones [120, 121], hydroxy lactones [722, 123], hydroxy lactams [124] and hydroxy nitriles [725] into fluoro esters, fluoro ketones, fluoro lactones, fluoro lactams, and fluoro nitnles, respectively (equations 60-63)... 

The formation of a-amino nitrile 2 is likely to proceed via a cyanohydrin 4 (an a-hydroxy nitrile) as intermediate, which is formed by the addition of hydrogen cyanide to the aldehyde 1 ... 

Hydroxy-nitrile (Cyanhydrine) werden am besten mit Diboran reduziert z.B.2 ... 

Lithiumboranat (sowie Calciumboranat) reduziert dagegen nur die Alkoxycarbonyl-Gruppe, und man erhalt a>-Hydroxy-nitrile. 

Hydroxy-2-formyl- -lacton 360 4-Hydroxy- -nitril 604 4-Hydroxy-3-oxo- -methylester 204 4-Hydroxy-4-phenyl- -lacton... 

The addition of HCN to aldehydes or ketones produces cyanohydrins (a-hydroxy nitriles). Cyanohydrins racemize under basic conditions through reversible loss of FiCN as illustrated in Figure 6.30. Enantiopure a-hydroxy acids can be obtained via the DKR of racemic cyanohydrins in the presence of an enantioselective nitriletransforming enzyme [86-88]. Many nitrile hydratases are metalloenzymes sensitive to cyanide and a nitrilase is usually used in this biotransformation. The DKR of mandelonitrile has been extended to an industrial process for the manufacture of (R)-mandelic acid [89]. 

Nitrile oxides are usually prepared via halogenation and dehydrohalogenation of aldoximes [11] or via dehydration of primary nitro alkanes (Scheme 1) [12]. However, it is important to note that nitrile oxides are relatively unstable and are prone to dimerization or polymerization, especially upon heating. 1,3-Dipolar cycioaddition of a nitrile oxide with a suitable olefin generates an isoxazoline ring which is a versatile synthetic intermediate in that it provides easy access to y-amino alcohols, )5-hydroxy ketones, -hydroxy nitriles, unsaturated oximes, and a host of other multifunctional molecules (Scheme 1) [5a]. Particularly for the formation of )5-hydroxy ketones, nitrile oxide-olefin cycioaddition serve as an alternative to the Aldol reaction. 

The DKR of functionalized alcohols such as diols, hydroxy esters, hydroxy aldehydes, azido alcohols and hydroxy nitriles was also taken up as the synthetic uhlity of the products is very high besides such a study will bring out the effect of multifunctional substrates under these reaction conditions to broaden the scope of DKR. Initially, the DKR of diols was achieved with diruthenium catalyst 1... 

The DKRs of (J-azido alcohols and p-hydroxy nitriles were also accomplished hy employing 1 and CALB with PCPA as the acyl donor. The DKRs of p-azido alcohols were performed at 60°C while those of (3-hydroxy nitriles required higher temperature (100°C) primarily to enhance the racemization rate. The optical purities of products were satisfactory in all cases. In the case of p-hydroxy nitriles, dehydrogenation lowered the yield. 

In 1989, Isayama and Mukaiyama reported a related Co-catalyzed coupling reaction that employs a,b-unsaturated nitriles, amides, and esters with PhSiLb as a hydrogen source [9]. Cobalt-bis(diketonato) complex, Co(II)(dpm)2 [dpm = bis(dipivaloylmethanato)] (5mol%), exhibited high catalytic activity at 20 °C in the coupling of excess acrylonitrile and ben-zaldehyde to provide b-hydroxy nitrile 4 in 93% yield (syn anti = 50 50) (Scheme 5). N,N-Dimethylacrylamide and methyl cinnamate both reacted... 

Primary nitro compounds are good precursors for preparing nitriles and nitrile oxides (Eq. 6.31). The conversion of nitro compounds into nitrile oxides affords an important tool for the synthesis of complex natural products. Nitrile oxides are reactive 1,3-dipoles that form isoxazolines or isoxazoles by the reaction with alkenes or alky nes, respectively. The products are also important precursors for various substrates such as P-amino alcohols, P-hydroxy ketones, P-hydroxy nitriles, and P-hydroxy acids (Scheme 6.3). Many good reviews concerning nitrile oxides in organic synthesis exist some of them are listed here.50-56 Applications of organic synthesis using nitrile oxides are discussed in Section 8.2.2. 

The nitrile-hydrolyzing activity of Ar throb act er spp. NS SC 104 was shown to be resistant to the suppressing effect of a-hydroxy nitriles such as lactonitrile and HMTBN, and accumulated the corresponding a-hydroxy acid ammonium salt at a high concentration [77]. HMTBN (200 him) was added to a suspension of Ar throb act er spp. NSSC 104 cells (4% dew) in phosphate buffer (0.1 m, pH 7.5) and mixed at 30 °C seven more additions of the same amount of HMTBN were added at 1 h intervals, then a further eight additions made at 1.5 h intervals over a total reaction time of 19 h. At completion of the reaction, the concentration of 2-hydroxy-4-methylthiobutyrate... 

The nitrilase from cyanobacterium Synechocystis sp. PCC6803 was found to effect the stereoselective hydrolysis of phenyl-substituted /3-hydroxy nitriles to (S)-enriched /3-hydroxy carboxylic acids. The enzyme also effected the conversion of y-hydroxynitrile, albeit with lesser enantioselectivity (Table 8.10). Interestingly, this enzyme was also was found to hydrolyze aliphatic dinitriles, such that for 1,2-dicyanoethane and 1,3-dicyanopropane the... 

Treatment of isoxazoline-fiised [60]fullerene 48 with NaOMe in the presence of MeOH gave the p-hydroxy nitrile derivative 49 in good yield <00SL361>. The synthesis of the enantiomerically pure cyclopropane amino acid 51 covalently attached to a fulleroisoxazoline has been achieved . 

The hydroxynitrile lyase (HNL)-catalysed cyanohydrin reaction is a useful method to synthesize enantiopure a-hydroxy nitriles and the corresponding a-hydroxy acids. However, small ketones, such as 2-butanone, are converted with low selectivities, due to the poor discrimination between methyl and ethyl. ... 

Nanda, S., Kato, Y. and Asano, Y., A new (i )-hydroxy-nitrile lyase from Prunus mume asymmetric synthesis of cyanohydrins. Tetrahedron, 2005, 61, 10908. 

Enzymes for Carboligation - 2-Ketoacid Decarboxylases and Hydroxy nitrile Lyases 333... 

Recently, Verkade and coworkers have reported the successful synthesis of /3-hydroxy-nitriles from carbonyl compounds in a reaction promoted by strong nonionic bases, such as proazaphosphatrane types. The reaction occurs in the presence of magnesium sulfate. 

Since 2000, atorvastatin (1) has been the world s top selling prescription drug, with sales in the 12 months to June 2008 of 13.8 billion [4]. The conversion of the chloro alcohol 2 to the key atorvastatin intermediate hydroxy nitrile 3 (Scheme 11.1) provides a good case history for the development of a continuous process, as it demonstrates... 

Cyanohydrins and their derivatives (see also Hydroxy nitriles) Bromodimethylborane, 47 Cyanotrimethylsilane, 87 B-3-Pinanyl-9-borabicyclo[3.3.1]nonane, 249... 

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